Intercellular arc signaling regulates vasodilation

June Bryan de la Peña, Paulino Barragan-Iglesias, Tzu Fang Lou, Nikesh Kunder, Sarah Loerch, Tarjani Shukla, Lokesh Basavarajappa, Jane Song, Dominique N. James, Salim Megat, Jamie K. Moy, Andi Wanghzou, Pradipta R. Ray, Kenneth Hoyt, Oswald Steward, Theodore J. Price, Jason Shepherd, Zachary T. Campbell

Research output: Contribution to journalArticlepeer-review

Abstract

Injury responses require communication between different cell types in the skin. Sensory neurons contribute to inflammation and can secrete signaling molecules that affect non-neuronal cells. Despite the pervasive role of translational regulation in nociception, the contribution of activity-dependent protein synthesis to inflammation is not well understood. To address this problem, we examined the landscape of nascent translation in murine dorsal root ganglion (DRG) neurons treated with inflammatory mediators using ribosome profiling. We identified the activity-dependent gene, Arc, as a target of translation in vitro and in vivo. Inflammatory cues promote local translation of Arc in the skin. Arc-deficient male mice display exaggerated paw temperatures and vasodilation in response to an inflammatory challenge. Since Arc has recently been shown to be released from neurons in extracellular vesicles (EVs), we hypothesized that intercellular Arc signaling regulates the inflammatory response in skin. We found that the excessive thermal responses and vasodilation observed in Arc defective mice are rescued by injection of Arc-containing EVs into the skin. Our findings suggest that activity-dependent production of Arc in afferent fibers regulates neurogenic inflammation potentially through intercellular signaling.

Original languageEnglish (US)
Pages (from-to)7712-7726
Number of pages15
JournalJournal of Neuroscience
Volume41
Issue number37
DOIs
StatePublished - Sep 15 2021

Keywords

  • Arc
  • DRG
  • Neuroinflamation
  • Nociceptors
  • Translational control

ASJC Scopus subject areas

  • Neuroscience(all)

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